Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: Radioligand binding assay and isolated tissue-based functional assay were used to evaluate affinity, potency, and receptor subtype selectivity of compounds. Inhibition of carbachol-induced increase in intravesicular pressure and salivary secretion were measured in anaesthetized rabbits to assess the functional selectivity. KEY RESULTS: In vitro radioligand binding study using human recombinant muscarinic receptors showed that AE9C90CB had greater affinity for M(3) muscarinic receptors with pKi of 9.90 +/- 0.11 and was 20-fold more selective for M(3) than for M(2) muscarinic receptors. AE9C90CB exhibited an unsurmountable antagonism on rat bladder strips (pK(B), 9.13 +/- 0.12). In anaesthetized rabbits after intravenous administration, AE9C90CB dose dependently inhibited carbachol-induced increase in intravesicular pressure and salivary secretion, and exhibited functional selectivity for urinary bladder over salivary gland which was ninefold better than that of oxybutynin. CONCLUSIONS AND IMPLICATIONS:
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Authors | S Sinha, S Gupta, S Malhotra, N S Krishna, A V Meru, V Babu, V Bansal, M Garg, N Kumar, A Chugh, A Ray |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 160
Issue 5
Pg. 1119-27
(Jul 2010)
ISSN: 1476-5381 [Electronic] England |
PMID | 20590605
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- AE9C90CB
- Bridged Bicyclo Compounds, Heterocyclic
- Muscarinic Antagonists
- Carbachol
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Topics |
- Animals
- Brain
(metabolism)
- Bridged Bicyclo Compounds, Heterocyclic
(administration & dosage, pharmacology)
- CHO Cells
- Carbachol
(antagonists & inhibitors)
- Cell Line, Transformed
- Cricetinae
- Cricetulus
- Dose-Response Relationship, Drug
- Female
- Humans
- Injections, Intravenous
- Male
- Mice
- Muscarinic Antagonists
(pharmacology)
- Rabbits
- Rats
- Salivary Glands
(drug effects)
- Urinary Bladder, Overactive
(drug therapy)
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